Cancers Of Other Organs Research Articles

Second malignancy in advanced or recurrent non-small cell lung cancer after the advent of molecular targeted drugs and immunotherapy.

This study aimed to investigate the characteristics of patients with recurrent or advanced non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) or immune-checkpoint inhibitors (ICIs) who developed secondary malignancies, as well as evaluate the impact of these secondary malignancies on the course of lung cancer. This study included 112 patients with postoperative recurrent or advanced NSCLC, who received TKIs, ICIs, or immune combination therapy as the primary treatment modality between April1, 2013, and March 31, 2020, and achieved long-term survival (≥2 years). Secondary malignancies were defined as newly diagnosed cancers in other organs occurring after NSCLC treatment initiation. Among the 112 patients, 10 (8.9%) developed 12 carcinomas, including third primary malignancies. Univariate analysis, considering secondary malignancies as the outcome, revealed a non-significant trend towards a higher incidence of secondary malignancies in smokers compared to non-smokers. This study found that 8.9% of patients with advanced NSCLC who received TKIs, ICIs, or immune combination therapy and survived ≥2 years developed secondary malignancies. This underscores the importance of early diagnosis and treatment, even during lung cancer treatment, to identify suspicious lesions in other organs either via imaging or physical examinations.

A case of lung metastasis from gastric cancer presenting as ground-glass opacity dominant nodules

BackgroundMost metastatic lung tumors present as solid nodules on chest computed tomography (CT). In contrast, ground-glass opacity on chest computed tomography usually suggests low-grade malignant lesions such as adenocarcinoma in situ or atypical adenomatous hyperplasia of the lung.Case presentationA 75-year-old woman with a history of gastric cancer surgery approximately 5 years prior was referred to the Department of Thoracic Surgery at our hospital because of two newly appearing pulmonary ground-glass opacity-dominant nodules on chest computed tomography. She had two ground-glass opacities in the right lower lobe, one in the S6 segment was 12 mm and the other in the S10 segment was 8 mm. On chest computed tomography 15 months prior to referral, the lesion in the S6 segment was 8 mm, and the lesion in the S10 segment was 2 mm. She was suspected to have primary lung cancer and underwent wide-wedge resection of the nodule in the S6 segment. In the resected specimen, polygonal tumor cells infiltrated the alveolar septa, with some tumor cells exhibiting signet ring cell morphology. Based on morphological similarities to the tumor cells of previous gastric cancers and the results of immunostaining, the patient was diagnosed with lung metastases of gastric cancer.ConclusionsPulmonary nodules in patients with a history of cancer in other organs, even if ground-glass opacity is predominant, should also be considered for the possibility of metastatic pulmonary tumors if they are growing rapidly.

Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis

Breast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron–astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.

Alexithymia, emotion regulation and autistic traits in Familial adenomatous polyposis

IntroductionFamilial adenomatous polyposis (FAP) is a condition characterised by multiple polyps inside the colon or rectum, leading to colorectal cancer in all patients who do not perform prophylactic colectomy and a higher risk of cancer in other organs. Nevertheless, it has been reported that 14-48% of patients do not comply with regular endoscopic surveillance, which seems to be related to the lower levels of emotional distress observed in these patients. Also, APC gene polymorphisms have been described as being related to neurodevelopmental disorders, such as autism.ObjectivesTo study the prevalence of alexithymia, autistic traits and emotion regulation strategies in patients with FAP.MethodsWe conducted a cross-sectional study of patients with a genetic or clinical FAP diagnosis and assessed for alexithymia, autistic traits and emotion regulation using psychometric tests - Toronto Alexithymia Scale - 20 items (TAS-20), Autism-Spectrum Quotient Test (AQ) and Emotion Regulation Questionnaire (ERQ), respectively. The control group were patients with Lynch Syndrome. Statistical analysis was performed using SPSS vs.26.ResultsWe recruited a total of 20 patients (10 with FAP vs 10 with Lynch Syndrome). Nine patients were male (45%) versus 11 female (55%). The mean age was 53,35 years (SD 18,4). Half the sample presented a low educational level (equal or inferior to 4th grade).The overall prevalence of alexithymia was 65%, with an 80% prevalence in FAP patients and 50% in Lynch Syndrome. TAS-20 total score was higher in FAP patients (69,0 vs 60,7; p=0,68). Externally-oriented thinking subscale score was statistically higher in FAP patients (p=0,024).The overall prevalence of autistic traits was 25%, and the mean AQ score was higher in FAP (23,4; SD 4.97) compared to Lynch Syndrome patients (20,2; SD 5.57), but there were no statistically significant differences between the diagnoses (p=0,192).A moderate positive correlation exists between Total AQ and Total TAS (r=0.51; p=0.020).Concerning the scores obtained on the ERQ scale, most participants (14; 70%) use Expressive Suppression as a regulation strategy. Patients with Lynch Syndrome had higher scores than those with FAP, both in the Cognitive Reappraisal (4.22; SD 1.58 vs 4.28; SD 0.90) and Expressive Suppression (4.58; SD 1.08 vs 5.15; SD 1.03) domains.The average AQ score for patients who mostly use expressive suppression is significantly higher than for those who use cognitive reappraisal (23.86 (3.63) vs 17.00 (6.6); p=0.039).ConclusionsThe preliminary results of this study point to high levels of alexithymia and autistic traits in this population, and a higher tendency to regulate emotions by expressive suppression.The main limitation of the study was the small sample size, which reduced the power of the study to find statistically significant differences. Also, in future studies, a different control group should be considered.Disclosure of InterestNone Declared

A Study of the Risk Factors for 402 Patients with Esophageal Squamous Cell Carcinoma - A Retrospective Comparison with Health Checkup Participants.

Objective Esophageal cancer is a gastrointestinal cancer with a poor prognosis. However, it is curable and can be treated endoscopically if it is detected at an early stage. The objective of this study was to identify the factors that contribute to early detection. Methods From April 2011 to December 2019, we retrospectively investigated consecutive patients diagnosed with esophageal squamous cell carcinoma (ESCC) through upper gastrointestinal endoscopy at two hospitals of Kawasaki Medical University based on medical records. The factors contributing to the early detection of ESCC were investigated by comparing patients with ESCC with those undergoing health checkups in whom no organic lesions were found in the upper gastrointestinal tract on endoscopy (controls). Patients Factors contributing to early detection were examined in 402 ESCC cases and 391 sex- and age-matched controls, and early and advanced cancers were compared along with the risk factors for ESCC. Results A multivariate analysis showed that alcohol consumption and smoking, concomitant cancer of other organs, and a low body mass index (BMI) were factors associated with ESCC (odds ratio [OR], 4.65; 95% confidence interval [CI], 2.880-7.520, OR,3.63; 95% CI, 2.380-5.540, OR, 2.09; 95% CI, 1.330-3.270, OR, 6.38; 95% CI, 3.780-10.800), whereas dyslipidemia was significantly less common in patients with ESCC (OR, 0.545; 95% CI, 0.348-0.853). Comparing early and advanced cancers, a history of endoscopic screening was the only factor involved in early detection (OR, 7.93; 95% CI, 4.480-14.00). Conclusion The factors associated with ESCC include alcohol consumption, smoking, concomitant cancer of other organs, and a low BMI. Endoscopy in subjects with these factors may therefore be recommended for the early detection of ESCC.

Reactive oxygen species induced by indomethacin enhance accumulation of heme carrier protein 1 and hematoporphyrin accumulation in vitro and in vivo in a brain tumor model.

Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we showed that the production of cancer-specific reactive oxygen species from mitochondria (mitROS) leads in turn to enhanced HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concentrations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect.

Ultravision joins the fight against peritoneal cancer

Ultravision join the fight against peritoneal cancer Peritoneal metastases (PM) refers to cancer that has spread from primary cancer in other organs in the abdomen to the peritoneum, the membrane that lines the abdominal cavity. According to the WHO, there are over seven million new primary abdominal cancer cases each year (1), and depending upon the primary cancer, up to 60% of these will present evidence of PM. (2) As a result, it is estimated that every 30 seconds, a patient is diagnosed with peritoneal metastases. In most cases, at diagnosis, it is typically an advanced, incurable disease. Current therapy guidelines recommend palliative systemic chemotherapy. However, with poor blood supply to the peritoneum, efficacy is poor, and side effects are debilitating. As a result, this terrible disease has a poor prognosis, with patient survival worse than lung and liver metastases. (3) It remains a high, unmet medical need.

Incessant ovulation: a review of its importance in predicting cancer risk.

Estrous cycles are recurring changes in therian mammals induced by estrogen, progesterone, and other hormones culminating in endometrial proliferation, ovulation, and implantation if fertilization occurred. In women, the estrous cycle is the menstrual cycle; but, unlike most mammals, the end of an infertile cycle is marked by endometrial sloughing and the start of another without an anestrous phase. Women stop cycling at menopause, while in most mammals, cycles continue until death. Epidemiologic studies identified menarche, menopause, births, lactation, and oral contraceptive (OC) use as key risk factors for ovarian, breast, and endometrial cancers. A composite variable was created to estimate the number of cycles not interrupted by events that stop ovulation. Captured by the phrase "incessant ovulation", repetitive cycles were first postulated to affect ovarian cancer risk and later extended to breast and endometrial cancers. These associations could be explained by cumulative effects of repetitive tissue changes within reproductive organs, immune consequences of repetitive ovulation through the glycoprotein mucin 1, and residual effects of past ovulations that enhance ovarian production of testosterone. The latter two pathways could affect the risk for cancers in other organs not considered "reproductive".

New Perspectives on Sex Steroid Hormones Signaling in Cancer-Associated Fibroblasts of Non-Small Cell Lung Cancer.

The importance of sex hormones, especially estrogen, in the pathogenesis of non-small-cell lung cancer (NSCLC) has attracted attention due to its high incidence among young adults and nonsmokers, especially those who are female. Cancer-associated fibroblasts (CAFs) reside in the cancer stroma and influence cancer growth, invasion, metastasis, and acquisition of drug resistance through interactions with cancer cells and other microenvironmental components. Hormone-mediated cell-cell interactions are classic cell-cell interactions and well-known phenomena in breast cancer and prostate cancer CAFs. In cancers of other organs, including NSCLC, the effects of CAFs on hormone-receptor expression and hormone production in cancer tissues have been reported; however, there are few such studies. Many more studies have been performed on breast and prostate cancers. Recent advances in technology, particularly single-cell analysis techniques, have led to significant advances in the classification and function of CAFs. However, the importance of sex hormones in cell-cell interactions of CAFs in NSCLC remains unclear. This review summarizes reports on CAFs in NSCLC and sex hormones in cancer and immune cells surrounding CAFs. Furthermore, we discuss the prospects of sex-hormone research involving CAFs in NSCLC.

Prognosis of Patients with Esophageal Carcinoma After Routine Thoracic Duct Resection: A Propensity-matched Analysis of 12,237 Patients Based on the Comprehensive Registry of Esophageal Cancer in Japan.

To clarify whether routine thoracic duct (TD) resection improves the prognosis of patients with esophageal cancer after radical esophagectomy. Although TD resection can cause nutritional disadvantage and immune suppression, it has been performed for the resection of surrounding lymph nodes. We analyzed 12,237 patients from the Comprehensive Registry of Esophageal Cancer in Japan who underwent esophagectomy between 2007 and 2012. TD resection and preservation groups were compared in terms of prognosis, perioperative outcomes, and initial recurrent patterns using strict propensity score matching. Particularly, the year of esophagectomy and history of primary cancer of other organs were added as covariates. After propensity score matching, 1638 c-Stage I-IV patients participated in each group. The 5 year overall survival and cause-specific survival rates were 57.5% and 65.6% in the TD-resected group and 55.2% and 63.4% in the TD-preserved group, respectively, without significant differences. The TD-resected group had significantly more retrieved mediastinal nodes (30 vs 21, P < 0.0001) and significantly fewer lymph node recurrence (376 vs 450, P = 0.0029) compared with the TD-preserved group. However, the total number of distant metastatic organs was significantly greater in TD-resected group than in the TD-preserved group (499 vs 421, P = 0.0024). TD resection did not improve survival in patients with esoph-ageal cancer. Despite having retrieved more lymph nodes, TD resection caused distant metastases in more organs compared to TD preservation. Hence, prophylactic TD resection should not be recommended in patients with esophageal cancer.

Cuproptosis and its application in different cancers: an overview.

Heavy metal ions are essential micronutrients for human health. They are also indispensable to maintaining health and regular operation of organs. Increasing or decreasing these metal ions will lead to cell death, such as ferroptosis. Tsvetkov et al. have recently proposed a novel cell death method called "Cuproptosis". Many researchers have linked this form of death to the diagnosis, prognosis, microenvironment infiltration, and prediction of immunotherapeutic efficacy of various tumors to better understand these tumors. Similarly, with the proposal of this mechanism, the killing effect of copper ionophores on cancer cells has come to our attention again. We introduced the mechanism of cuproptosis in detail and described the establishment of the corresponding prognostic model and risk score for uveal melanoma through cuproptosis. In addition, we describe the current progress in the study of cancer in other organs through cuproptosis and summarize the treatment of tumours by copper ionophore and its future research direction. With further research, the concept of cuproptosis may help us understand cancer and guide its clinical treatment.

Effect of blood product transfusion on the prognosis of patients undergoing hepatectomy for hepatocellular carcinoma: a propensity score matching analysis.

Hepatectomy, the most common treatment for hepatocellular carcinoma, is associated with greater intraoperative blood loss than is resection of other malignancies. The effect of blood product transfusion (red blood cell [RBC], platelet, fresh frozen plasma [FFP], 5 and 25% albumin) on prognosis remains unclear. This study examined effects of blood product transfusion on prognoses of patients who underwent hepatectomy for hepatocellular carcinoma. We included 2015 patients with pathologically confirmed hepatocellular carcinoma who underwent hepatectomy at our institution during 1990-2019. Patients (n = 534) who underwent repeat hepatectomy, non-curative hepatectomy, those with synchronous cancer in other organs, those who died within 1month of surgery, and those with missing data were excluded. Finally, 1481 patients (1142 males, 339 females; median age: 68years) with curability A or B were included. Intraoperative blood loss (> 500mL) was an independent predictor of RBC transfusion (odds ratio, 8.482; P < 0.001). All transfusion groups had poorer recurrence-free survival (RFS) and overall survival (OS) than non-transfusion groups. After propensity score matching, the 5year RFS rate was 13.4 and 16.3% in the RBC and no-RBC groups, respectively (P = 0.020). The RBC group had a significantly lower 5year OS rate than the no-RBC group (42.1 vs. 48.8%, respectively; P = 0.035) and the FFP group (57.0%) than the no-FFP group (63.9%) (p = 0.047). No significant between-subgroup differences were found for other blood transfusion types. RBC transfusion promotes hepatocellular carcinoma recurrence and RBC/FFP transfusions reduced long-term survival and RFS and OS in patients who underwent radical liver resection of HCC.

Serum Mac-2 binding protein level predicts the development of liver-related events and colorectal cancer in patients with NAFLD.

We previously demonstrated that Mac‐2 binding protein (M2BP) is a useful biomarker for nonalcoholic fatty liver disease (NAFLD), particularly NAFLD fibrosis prediction. In the present study, we investigated the prognostic value of M2BP in patients with NAFLD. A total of 506 patients with biopsy‐confirmed NAFLD from 2002 to 2013 were enrolled in this study in Japan. Three hundred fifty‐three of these patients with NAFLD were available for follow‐up for more than 100 days and showed no liver‐related events at the time of entry. Liver‐related events were defined as hepatocellular carcinoma (HCC), decompensation, and gastroesophageal varices with variceal treatment. The mean follow‐up duration of all the subjects was 2716 ± 1621 days (102–7483 days). Eighteen patients developed new liver‐related events (HCC, 8; decompensation, 11; varices, 8). Nine patients developed cardiovascular disease (CVD), and 24 patients developed new cancers in other organs. The median serum M2BP level was 1.603 μg/mL, and we divided our cohort into two groups according to the serum M2BP level: M2BP low group (M2BP Low) and M2BP high group (M2BP Hi). The incidence of HCC was significantly higher in M2BP Hi (n = 8) than in M2BP Low (n = 0). The incidence of liver‐related events was significantly higher in M2BP Hi (n = 16) than in M2BP Low (n = 2). The incidences of death, CVD events, and cancer in other organs were not different between the groups. Interestingly, the incidence of colorectal cancer was significantly higher in M2BP Hi (n = 5) than in M2BP Low (n = 0). Conclusion: M2BP is a useful biomarker to predict liver‐related events, particularly HCC. Additionally, M2BP is a potential predictive biomarker of colorectal cancer development.

Effect of chemoradiation on the development of second primary cancers after endoscopic resection of T1 esophageal squamous cell carcinoma.

Patients with early esophageal squamous cell carcinoma (ESCC) may develop multiple second primary ESCC and cancers in other organs even after curative endoscopic resection (ER). We investigated whether administration of chemoradiotherapy (CRT) after ER decreases the incidence of second primary cancers. We conducted a post hoc analysis of the prospective study. Among the registered 170 patients with clinical submucosal ESCC, 74 underwent ER alone, and 96 underwent ER followed by CRT (ER + CRT) because of pathological results of submucosal or lympho-vascular invasion. We compared the incidence of second primary cancers in esophagus and in other organs between two treatment groups. A univariate analysis was performed to investigate the related risk factors. All patients were followed up with esophagogastroduodenoscopy and CT every 4months for the first 3years and every 6months thereafter. Sixty-one ESCC were detected in 32 patients, and the 3-year cumulative incidence of multiple ESCCs was not different between ER + CRT and ER alone (10.4% vs. 13.5%). Sixty-three second primary cancers in other organs were detected in 45 patients, and there was no difference in the cumulative incidence between two groups. The risk factors for multiple ESCCs were high alcohol consumption and grade C multiple Lugol-voiding lesions. Heavy drinker or patients with grade C multiple Lugol-voiding lesion rather than CRT were at risk for second primary ESCC. CRT after ER did not decrease the cumulative incidence of second primary ESCC nor cancers in other organs comparing with ER alone.

Survey of photoneutron emitted from 6MV, 10MV, and 15MV medical LINAC using nuclear track detection

Background: Medical linear accelerators (LINAC) can produce unwanted photoneutrons that might cause tissue damage or cancer in other organs. The efficient techniques and detectors are importantly required to detect these harmful neutrons. Objectives: This study aimed to measure photoneutrons produced from medical LINAC of 6, 10, and 15 megavolts (MV). Materials and methods: Nuclear track detector (CR-39 detectors) were employed to quantify the number of neutrons from LINACs. The X-ray energies, doses, and radiation techniques were varied to compare the number of neutrons. The photoneutron productions inside the LINAC room were also examined. Results: The results showed that there were no neutrons from medical LINAC 6 MV, whereas photoneutrons could be detected from 10 and 15 MV LINAC. Radiotherapeutic techniques with moving multi-leaf collimator (MLC) produced higher photoneutron than techniques without using MLC. The neutrons were detected on the walls of the LINAC room. Conclusion: X-ray energy greater than 10 MeV generated undesired photoneutrons that can penetrate the shielding and increase the patient dose. For the safety of staff to re-enter the treatment room, delaying time should be considered for the neutron decay process

Delta-He a new biomarker for a surgical clinic

Delta-He the difference between hemoglobin content in reticulocytes and erytrocytes is a relatively new laboratory indicator that is easily measured in everyday practice. This parameter is directly related to iron bioavailability for hemoglobin synthesis and can reflect various conditions accompanied by cytokine expression including systemic inflammation. To analyze the prospects for practical application of hemoglobin delta in assessment of neurosurgical patients throughout in-hospital treatment. We analyzed complete blood counts (Sysmex XN-1000 analyzer) with optical determination of reticulocyte hemoglobin and automatic calculation of Delta-He in 82 neurosurgical patients. Exclusion criteria were severe decompensated comorbidities, exacerbation of chronic infectious processes, cancer of other organs. Blood sampling for analysis of delta-hemoglobin was carried out before all diagnostic and therapeutic measures. Reference interval is indicated by the analyzer manufacturer as 1.7-4.4 pg. Delta-He values at admission ranged from -1.8 to 6.1 pg. There was a consistent decrease of these values throughout 3-4 postoperative days. Then, the values could increase or continued to decrease. Increment of the index was noted in 76 patients (92.7%). Such dynamics was observed in case of uncomplicated postoperative period. Further decrease of Delta-He was observed in 6 patients (7.3%). These ones were characterized by a longer recovery after surgery, and the events required additional medical or surgical correction were recorded. Negative dynamics of Delta-He values could precede clinical manifestations of certain complication. Clarification of diagnosis and correction of therapy were accompanied by gradual increase of Delta-He values. Estimation of Delta-He values over time can be used for monitoring of patients and effectiveness of therapy. From a practical point of view, it is important that examination can be performed at any time of the day.

Gender Disparities in Their Effects on Characteristics and Prognostics of Lung Cancer Patients in Pulmonary Ward of Dr. M Djamil Hospital, Padang

Background: Lung cancer incidence in female tends to increase in many countries. Various studies have reported the characteristics of lung cancer in female are different from male. The purpose of this study was to determine the effect of gender on characteristics of lung cancer at Dr. M Djamil Hospital, Padang.Methods: A retrospective analytic study of lung cancer patients treated in the Pulmonary Ward of Dr. M. Djamil Hospital Padang from January 1, 2004 to December 31, 2017, with recognized cancer cell types. Data were grouped according to gender.Results: This study found that 451 lung cancer patients, male-dominant 77.8%. Female were younger than male (52.97 ± 12.79 years vs. 57.81 ± 11.23 years; p = 0.00). Most of male (94.5%) were smokers and former smokers, while 93.9% of female were non-smokers (p = 0.00). Most female were having prior history of tuberculosis (TB) (21.2% vs 11.0%; p = 0.008) and also prior history of other organs cancer (10.1% vs 3.4%; p = 0.007) than in male. Squamous cells were highest in males (41.1%), while females had adenocarcinoma (55.0%); with p = 0.008. Advanced stage in female more than male (91.8% vs 82.7%; p = 0.027). The mean life expectancy of female was longer than male, respectively 8.74 ± 1.56 and 7.29 ± 0.64 months; (p = 0.95). Conclusion: There are differences in the epidemiology of lung cancer between male and female in Dr. M. Djamil Hospital Padang in the form of age, cell type and staging. Non-smokers, a previous history of TB and a history of cancer in other organs were more dominant in female.

The immunological and metabolic landscape in primary and metastatic liver cancer.

The liver is the sixth most common site of primary cancer in humans, and generally arises in a background of cirrhosis and inflammation. Moreover, the liver is frequently colonized by metastases from cancers of other organs (particularly the colon) because of its anatomical location and organization, as well as its unique metabolic and immunosuppressive environment. In this Review, we discuss how the hepatic microenvironment adapts to pathologies characterized by chronic inflammation and metabolic alterations. We illustrate how these immunological or metabolic changes alter immunosurveillance and thus hinder or promote the development of primary liver cancer. In addition, we describe how inflammatory and metabolic niches affect the spreading of cancer metastases into or within the liver. Finally, we review the current therapeutic options in this context and the resulting challenges that must be surmounted.

The blood-tumour barrier in cancer biology and therapy.

The protective blood-brain barrier has a major role in ensuring normal brain function by severely limiting and tightly controlling the ingress of substances into the brain from the circulation. In primary brain tumours, such as glioblastomas, as well as in brain metastases from cancers in other organs, including lung and breast cancers and melanoma, the blood-brain barrier is modified and is referred to as the blood-tumour barrier (BTB). Alterations in the BTB affect its permeability, and this structure participates in reciprocal regulatory pathways with tumour cells. Importantly, the BTB typically retains a heterogeneous capacity to restrict the penetration of many therapeutic agents into intracranial tumours, and overcoming this challenge is a key to improving the effectiveness of treatment and patient quality of life. Herein, current knowledge of BTB structure and function is reviewed from a cell and cancer biology standpoint, with a focus on findings derived from in vivo models and human tumour specimens. Additionally, how this knowledge can be translated into clinical advances for patients with cancer is discussed.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2020 for the Clinical Practice of Hereditary Colorectal Cancer

Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnosis, treatment or surveillance, from sporadic colorectal cancer management. There are two representative HCRC, named familial adenomatous polyposis and Lynch syndrome. Other than these two HCRC syndromes, related disorders have also been reported. Several guidelines for hereditary disorders have already been published worldwide. In Japan, the first guideline for HCRC was prepared by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), published in 2012 and revised in 2016. This revised version of the guideline was immediately translated into English and published in 2017. Since then, several new findings and novel disease concepts related to HCRC have been discovered. The currently diagnosed HCRC rate in daily clinical practice is relatively low; however, this is predicted to increase in the era of cancer genomic medicine, with the advancement of cancer multi-gene panel testing or whole genome testing, among others. Under these circumstances, the JSCCR guidelines 2020 for HCRC were prepared by consensus among members of the JSCCR HCRC Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR guidelines 2020 for HCRC.